European Published Application 595,557 (published May 4, 1994) discloses novel substituted azetidinones of the general formula 1 as potent elastase inhibitors, which are useful as anti-inflammatory and anti-degenerative agents. These compounds may be used in the treatment of inflammatory conditions resulting in connective tissue destruction, e.g. rheumatoid arthritis, emphysema, bronchial inflammation, chronic bronchitis, glomerulonephritis, osteoarthritis, spondylitis, lupus, psoriasis, atherosclerosis, sepsis, septicemia, shock, myocardial infarction, reperfusion injury, periodonitis, cystic fibrosis and acute respiratory distress syndrome. ##STR1##
A subset of compounds disclosed in EP 595,557 are those wherein R and R.sup.1 are each ethyl, R.sub.4 is a carboxylic acid derivative such as a carboxamide, and the absolute configuration at carbon-4 of the azetidinone ring is S (1a) ##STR2## These compounds are exemplified by the compound of formula 2. ##STR3##
The synthesis of compounds of formula 1 a requires the chiral intermediate of formula I ##STR4##
The chiral compound I may be obtained from a racemic mixture using conventional chemical process such as by formation of a salt with an optically active base, followed by separation of the resultant diastereomers, for example by fractional crystallization. However, the chemical resolution process is generally long and tedious, and it would be advantageous if a more convenient method is available for the preparation of chiral compound I.